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Journal of Virology, December 2008, p. 11705-11713, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01320-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement{triangledown}

Zhili Xu, Jie Tian, Jeffrey S. Smith, and Andrew P. Byrnes*

Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 24 June 2008/ Accepted 16 September 2008

Kupffer cells (KCs) rapidly remove intravenously injected adenovirus (Ad) vectors from the circulation. A better understanding of the mechanisms involved could suggest strategies to improve Ad gene delivery by suppressing or evading KC uptake. We recently showed that clearance of Ad type 5 vectors by KCs does not involve the interaction of Ad with the well-established Ad receptors, namely, integrins or the coxsackievirus and Ad receptor (J. S. Smith, Z. Xu, J. Tian, S. C. Stevenson, and A. P. Byrnes, Hum. Gene Ther. 19:547-554, 2008). In the current study, we systematically quantified the contributions of various receptors and plasma proteins to the clearance of Ad by KCs. We found that scavenger receptors are a predominant mechanism for the clearance of Ad by KCs. In addition, we found that Ad is opsonized by natural immunoglobulin M antibodies and complement and that these opsonins play a contributory role in the clearance of Ad by KCs. We also examined additional mechanisms that have been postulated to be involved in the clearance of Ad, including the binding of Ad to platelets and vitamin K-dependent coagulation factors, but we found that neither of these were required for the clearance of Ad by KCs.

* Corresponding author. Mailing address: Division of Cellular and Gene Therapies, FDA/CBER, HFM-725, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 827-1786. Fax: (301) 827-0449. E-mail: Andrew.Byrnes{at}fda.hhs.gov

{triangledown} Published ahead of print on 24 September 2008.

Journal of Virology, December 2008, p. 11705-11713, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01320-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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